The Gap Junction Inhibitor Octanol Decreases Proliferation and Increases Glial Differentiation of Postnatal Neural Progenitor Cells.

Neural precursor cells (NPCs) that persist in the postnatal/adult subventricular zone (SVZ) express connexins that form hemichannels and gap junctions. Gap junctional communication plays a role in NPC proliferation and differentiation during development, but its relevance on postnatal age remains to be elucidated. In this work we aimed to evaluate the effect of the blockade of gap junctional communication on proliferation and cell fate of NPCs obtained from the SVZ of postnatal rats.

Antiproliferative effect of boldine on neural progenitor cells and on glioblastoma cells.

Introduction: The subventricular zone (SVZ) is a brain region that contains neural stem cells and progenitor cells (NSCs/NPCs) from which new neurons and glial cells are formed during adulthood in mammals. Recent data indicate that SVZ NSCs are the cell type that acquires the initial tumorigenic mutation in glioblastoma (GBM), the most aggressive form of malignant glioma. NSCs/NPCs of the SVZ present hemichannel activity whose function has not yet been fully elucidated.

Purinergic Receptor Blockade with Suramin Increases Survival of Postnatal Neural Progenitor Cells In Vitro.

Neural progenitor cells (NPCs) are self-renewing and multipotent cells that persist in the postnatal and adult brain in the subventricular zone and the hippocampus. NPCs can be expanded in vitro to be used in cell therapy. However, expansion is limited, since the survival and proliferation of adult NPCs decrease with serial passages.

To Become or Not to Become Tumorigenic: Subventricular Zone Hippocampal Neural Stem Cells.

Neural stem cells (NSCs) persist in the adult mammalian brain in two neurogenic regions: the subventricular zone lining the lateral ventricles and the dentate gyrus of the hippocampus. Compelling evidence suggests that NSCs of the subventricular zone could be the cell type of origin of glioblastoma, the most devastating brain tumor. Studies in glioblastoma patients revealed that NSCs of the tumor-free subventricular zone, harbor cancer-driver mutations that were found in the tumor cells but were not present in normal cortical tissue.

Connexin43 Region 266-283, via Src Inhibition, Reduces Neural Progenitor Cell Proliferation Promoted by EGF and FGF-2 and Increases Astrocytic Differentiation.

Neural progenitor cells (NPCs) are self-renewing cells that give rise to the major cells in the nervous system and are considered to be the possible cell of origin of glioblastoma. The gap junction protein connexin43 (Cx43) is expressed by NPCs, exerting channel-dependent and -independent roles. We focused on one property of Cx43-its ability to inhibit Src, a key protein in brain development and oncogenesis.

Extracellular Vesicle-Mediated Communication between the Glioblastoma and Its Microenvironment.

The glioblastoma is the most malignant form of brain cancer. Glioblastoma cells use multiple ways of communication with the tumor microenvironment in order to tune it for their own benefit. Among these, extracellular vesicles have emerged as a focus of study in the last few years.

Neural Stem Cells of the Subventricular Zone as the Origin of Human Glioblastoma Stem Cells. Therapeutic Implications.

Human glioblastoma is the most aggressive type of primary malignant brain tumors. Standard treatment includes surgical resection followed by radiation and chemotherapy but it only provides short-term benefits and the prognosis of these brain tumors is still very poor. Glioblastomas contain a population of glioma stem cells (GSCs), with self-renewal ability, which are partly responsible for the tumor resistance to therapy and for the tumor recurrence after treatment.

Interactions Between Neural Progenitor Cells and Microglia in the Subventricular Zone: Physiological Implications in the Neurogenic Niche and After Implantation in the Injured Brain.

The adult subventricular zone (SVZ) of the mammalian brain contains neural progenitor cells (NPCs) that continuously produce neuroblasts throughout life. These neuroblasts migrate towards the olfactory bulb where they differentiate into local interneurons. The neurogenic niche of the SVZ includes, in addition to NPCs and neuroblasts, astrocytes, ependymal cells, blood vessels and the molecules released by these cell types.

Functional Diversity of Neurotrophin Actions on the Oculomotor System.

Neurotrophins play a principal role in neuronal survival and differentiation during development, but also in the maintenance of appropriate adult neuronal circuits and phenotypes. In the oculomotor system, we have demonstrated that neurotrophins are key regulators of developing and adult neuronal properties, but with peculiarities depending on each neurotrophin. For instance, the administration of NGF (nerve growth factor), BDNF (brain-derived neurotrophic factor) or NT-3 (neurotrophin-3) protects neonatal extraocular motoneurons from cell death after axotomy, but only NGF and BDNF prevent the downregulation in ChAT (choline acetyltransferase).

Neural progenitor cells isolated from the subventricular zone present hemichannel activity and form functional gap junctions with glial cells.

The postnatal subventricular zone (SVZ) lining the walls of the lateral ventricles contains neural progenitor cells (NPCs) that generate new olfactory bulb interneurons. Communication via gap junctions between cells in the SVZ is involved in NPC proliferation and in neuroblast migration towards the olfactory bulb. SVZ NPCs can be expanded in vitro in the form of neurospheres that can be used for transplantation purposes after brain injury.

Neural progenitor cell implants in the lesioned medial longitudinal fascicle of adult cats regulate synaptic composition and firing properties of abducens internuclear neurons.

Transplants of neural progenitor cells (NPCs) into the injured CNS have been proposed as a powerful tool for brain repair, but, to date, few studies on the physiological response of host neurons have been reported. Therefore, we explored the effects of NPC implants on the discharge characteristics and synaptology of axotomized abducens internuclear neurons, which mediate gaze conjugacy for horizontal eye movements. NPCs were isolated from the subventricular zone of neonatal cats and implanted at the site of transection in the medial longitudinal fascicle of adult cats.

Implanted neural progenitor cells regulate glial reaction to brain injury and establish gap junctions with host glial cells.

Transplantation of neural stem/progenitor cells (NPCs) in the lesioned brain is able to restore morphological and physiological alterations induced by different injuries. The local microenvironment created at the site of grafting and the communication between grafted and host cells are crucial in the beneficial effects attributed to the NPC implants. We have previously described that NPC transplantation in an animal model of central axotomy restores firing properties and synaptic coverage of lesioned neurons and modulates their trophic factor content.

Neural progenitor cell implants modulate vascular endothelial growth factor and brain-derived neurotrophic factor expression in rat axotomized neurons.

Axotomy of central neurons leads to functional and structural alterations which largely revert when neural progenitor cells (NPCs) are implanted in the lesion site. The new microenvironment created by NPCs in the host tissue might modulate in the damaged neurons the expression of a high variety of molecules with relevant roles in the repair mechanisms, including neurotrophic factors. In the present work, we aimed to analyze changes in neurotrophic factor expression in axotomized neurons induced by NPC implants.

Differential regulation of the expression of neurotrophin receptors in rat extraocular motoneurons after lesion.

Neurotrophins acting through high-affinity tyrosine kinase receptors (trkA, trkB, and trkC) play a crucial role in regulating survival and maintenance of specific neuronal functions after injury. Adult motoneurons supplying extraocular muscles survive after disconnection from the target, but suffer dramatic changes in morphological and physiological properties, due in part to the loss of their trophic support from the muscle. To investigate the dependence of the adult rat extraocular motoneurons on neurotrophins, we examined trkA, trkB, and trkC mRNA expression after axotomy by in situ hybridization.

Respiratory response to systemic inhibition of the Na+/H+ exchanger type 3 in intact rats.

The Na+/H+ exchangers (NHEs) are a family of antiporters involved in the maintenance of neural steady-state intracellular pH. The NHE3 seems to be the predominant subtype in central chemosensitive cells. We aimed to analyze the effect of a selective NHE3 inhibition on the respiratory pattern in spontaneously breathing rats with intact vagi.

Nitric oxide decreases subventricular zone stem cell proliferation by inhibition of epidermal growth factor receptor and phosphoinositide-3-kinase/Akt pathway.

Nitric oxide (NO) inhibits proliferation of subventricular zone (SVZ) neural precursor cells in adult mice in vivo under physiological conditions. The mechanisms underlying this NO effect have now been investigated using SVZ-derived neural stem cells, which generate neurospheres in vitro when stimulated by epidermal growth factor (EGF). In these cultures, NO donors decreased the number of newly formed neurospheres as well as their size, which indicates that NO was acting on the neurosphere-forming neural stem cells and the daughter neural progenitors.

Enhanced c-Fos expression in the rostral ventral respiratory complex and rostral parapyramidal region by inhibition of the Na+/H+ exchanger type 3.

Previous studies have shown that selective inhibition of Na+/H+ exchanger type 3 (NHE3) induces intracellular acidification and activates CO2/H+-sensitive medullary neurons, mimicking the responses evoked by hypercapnic stimuli. In addition, NHE3 blockers administration decreases the duration of apnoea induced by laryngeal stimulation, presumably by means of central chemoreceptor activation. To test the hypothesis that the central chemoreceptor network may be affected by NHE3 inhibition, brainstem c-Fos immunoreactive cell counting was performed after systemic administration of the NHE3 blocker AVE1599 (Aventis Pharma Deutschland GmbH) (2 mg/kg).

Role of nitric oxide in subventricular zone neurogenesis.

A possible role of nitric oxide (NO) in adult neurogenesis has been suggested based on anatomical findings showing that subventricular zone (SVZ) neuroblasts are located close to NO-producing cells, and on the known antiproliferative actions of NO in many cell types. Experiments have been performed in rodents with systemic and intracerebroventricular administrations of the NO synthase (NOS) inhibitor L-NAME. NOS inhibition leads to significant increases in the number of proliferating cells in the SVZ and olfactory bulb (OB).

Nitric oxide is a physiological inhibitor of neurogenesis in the adult mouse subventricular zone and olfactory bulb.

The subventricular zone of the rodent brain retains the capacity of generating new neurons in adulthood. The newly formed neuroblasts migrate rostrally toward the olfactory bulb, where they differentiate as granular and periglomerular interneurons. The reported presence of differentiated neurons expressing the neuronal isoform of nitric oxide synthase (NOS) in the periphery of the neurogenic region and the organization of their varicose axons as a network in which the precursors are immersed raised the hypothesis that endogenous nitric oxide (NO) may participate in the control of neurogenesis in the subventricular zone.

Nitric oxide synthesis inhibition increases proliferation of neural precursors isolated from the postnatal mouse subventricular zone.

The subventricular zone (SVZ) of rodents retains the capacity to generate new neurons throughout the entire life of the animal. Neural progenitors of the SVZ survive and proliferate in vitro in the presence of epidermal growth factor (EGF). Nitric oxide (NO) has been shown to participate in neural tissue formation during development and to have antiproliferative actions, mediated in part by inhibition of the EGF receptor.

CGP 3466 increases survival of cultured fetal dopaminergic neurons.

Purpose: To analyze the effects of CGP 3466, a compound structurally related to deprenyl, on survival and function of fetal ventral mesencephalic dopaminergic neurons.

Methods: Free-floating roller tube (FFRT) cultures of rat (E14) ventral mesencephalon were treated with CGP 3466 [10-8 M] for 7 days. Tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) immunocytochemistry was performed to allow analysis of dopaminergic neurons and astroglial cells, respectively.

Antiproliferative effect of nitric oxide on epidermal growth factor-responsive human neuroblastoma cells.

Addition of nitric oxide (NO) donors to NB69 neuroblastoma cells produced a cGMP-independent decrease in cell proliferation, without affecting cell viability or apoptosis. The potency of short half-life NO donors was higher when cell proliferation was stimulated by epidermal growth factor (EGF), as compared with cultures exposed to fetal calf serum (FCS). Immunoprecipitation and western blot analysis of the EGF receptor (EGFR) revealed a significant reduction of its EGF-induced tyrosine phosphorylation in cells treated with the NO donor 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA-NO).